Androgen deprivation therapy and dementia risk: An updated and dose-response meta-analysis.

BackgroundThe association between androgen deprivation therapy (ADT) and dementia risk is controversial, and the dose-response relationship between them remains unclear.ObjectiveWe aim to further clarify the relationship between ADT and dementia risk.MethodsPubMed, Web of Science, Embase, and Cochrane Library databases were systematically searched up to September 2024 to identify relevant studies. A meta-analysis was conducted using hazard ratios (HR) and 95% confidence intervals (CI) as pooled indicators. The robust error meta-regression (REMR) approach was performed to explore the dose-response relationship. Heterogeneity was assessed using I² statistics, and subgroup analysis, sensitivity analysis, and meta-regressions were conducted. Publication bias was evaluated with a funnel plot and Egger's test.ResultsOur meta-analysis of 21 studies involving 2,278,835 patients revealed that ADT significantly increased the risk of overall dementia (HR = 1.14, 95% CI: 1.06-1.20) and Alzheimer's disease (AD) (HR = 1.15, 95% CI: 1.06-1.23), but not non-AD dementia (HR = 1.01, 95% CI: 0.89-1.16). For ADT subtypes, anti-androgens increased the risk of overall dementia (HR = 1.27, 95% CI: 1.09-1.49), particularly for AD (HR = 1.53, 95% CI: 1.19-1.97), while Luteinizing hormone-releasing hormone therapy and bilateral orchiectomy were not linked to the risk of any dementia subtype. A bell-shaped non-linear relationship between ADT duration and dementia risk was observed, with the highest risk observed at 15.5 to 21.5 months (HR = 1.25), which was confirmed by subgroup analysis for AD.ConclusionsThe risk of overall dementia and AD were found to be significantly associated with ADT in a bell-shaped dose-response effect.